A promising and widely studied example of vertebrate synaptic plasticity is long-term potentiation (LTP), the persistent synaptic enhancement seen following a brief period of coincident pre- and postsynaptic activity. It has been suggested that the cellular and molecular mechanisms responsible for LTP will elucidate several physiological phenomena including cognitive functions such as learning a memory. Understanding the mechanisms underlying LTP is important in deciphering the effects of experience on behavior and thus will likely give insight into the cellular basis of psychiatric diseases. The cellular signaling responsible for generating LTP in CA1 hippocampus has been studied extensively with no general consensus on the nature of the persistent modifications. This project will focus on testing a recent model proposed for LTP: synapses that have only functional NMDA receptors (and are silent at hyperpolarized potentials) acquire functional AMPA receptors during LTP. This possible mechanism of potentiation is import because it can incorporate virtually all results that have previously led to disparate views regarding the locus of modification during LTP in CA1 hippocampus. This model will be tested using electrophysiological and analytical techniques previously developed. In addition, rapid photolysis of caged glutamate will be used to mimic synaptic transmitter release. With these techniques four specific aims will be addressed. 1. Determine the prevalence of postsynaptically silent synapses in different nueronal types and at different points in development. 2. Determine if the changes observed during LTP are different at different points in development. 3. Determine if there is an increased sensitivity to photolytically delivered transmitter during LTP, 4. Determine the biophysical basis for postsynatically silent synapses. It is hoped that a detailed knowledge of the changes during LTP will elucidate the sites of synaptic modulation in physiological conditions as well as point to critical mechanisms that may be perturbed in pathologicalstates.